The present invention relates to an improved enterosoluble hard capsule containing a medicament.
As may be needless to say, what is meant by the term of enterosoluble medicamental hard capsule is, as the first meaning, a capsulated drug form orally administrated which is expected to release the active ingredient contained therein only when it has arrived at the intestinal canals. Along with the enterosoluble tablets, enterosoluble medicamental hard capsules belong to a class of enterosoluble medicaments and are widely used owing to the secondary effects of preventing inactivation of the active ingredient by the gastric juice and preventing troubles of and digestion impediment in the stomach by the ingredient as well as increasing the effective concentration of the active ingredient in the intestinal canals and extending the effective time of the ingredient.
Enterosoluble medicamental hard capsules are usually prepared by providing enterosoluble coating films on to the surface of a hard capsule for medicament use made of gelatine or the like which has been sealed after filling with a desired medicamental ingredient. The film-forming enterosoluble substances used in the above coating include copolymers of unsaturated carboxylic acids such as copolymers of methacrylic acid and methyl methacrylate and phthalic acid or succinic acid esters of certain cellulose derivatives such as cellulose acetate phthalate, hydroxypropylmethylcellulose phthalate, methylcellulose phthalate, cellulose acetate succinate and the like.
An alternative way for rendering a gelatine hard capsule enterosoluble is a method in which the outer surface of the gelatine capsule is treated with formalin so as that the solubility of the capsule in the gastric juice is decreased.
Both of the above described methods utilize the principle of imparting enteric solubility to the outer surface of an inherently gastrosoluble gelatine hard capsule by a secondary treatment. These methods have, accordingly, several defective points not only in the complicated process of the secondary treatment but also in the somewhat doubtful effectiveness of the enterosolubility imparted by the treatment. For example, the enterosoluble coating films formed on the surface of the gelatine capsules suffer from incomplete adhesive bonding between the enterosoluble coating films and the gelatine surface as well as gradual loss of the enterosolubility performance in the lapse of time, probably, due to the hydrolysis or other undesirable reaction which the enterosoluble substance undergoes with the moisture contained in the gelatine.
Further, the method of decreasing the solubility of gelatine by the formalin treatment is a delicate process so that a desired degree of enterosolubility is obtained with extreme difficulties even with a most careful process control.
It has been recently proposed that hard capsules are shaped with a substance which in itself is enterosoluble as exemplified by the above named copolymers or cellulose derivatives for enterosoluble coating films. These capsules made of an enterosoluble substance are promising from the practical standpoint since enterosoluble capsulated medicaments can be prepared by merely filling the capsule with the desired active ingredient without the necessity of the secondary treatment although there are several remaining problems in the enterosoluble capsules of this type with respect to the fragility and insufficient flexibility of the capsule shells and the toxicity of the additives such as a plasticizer usually incorporated in the capsule materials.
Despite the very wide prevalence of administering patients with enterosoluble capsulated medicaments with a therapeutic purpose, it is very often experienced in the actual clinic treatment that the exhibition of the effectiveness of the active ingredient contained in the enterosoluble hard capsules is unduly or irregularly delayed for an unknown reason so that the expected effect of the medicine in therapy or protection is obtained insufficiently or only with great variation in the effectiveness. This undesirable phenomenon of delayed exhibition of the effect of medicine appears not only in the case of administration after meal but also in the case of administration before meal.